JNK-interacting leucine zipper protein is a novel scaffolding protein in the Galpha13 signaling pathway.
JNK-interacting leucine zipper protein is a novel scaffolding protein in the Galpha13 signaling pathway.
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JNK 相互作用的亮氨酸拉链蛋白是 Galpha13 信号通路中的一种新型支架蛋白。
DOI：
10.1021/bi050604l
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发表时间：
2005
期刊：
影响因子：
--
通讯作者：
Dhanasekaran,DannyN
中科院分区：
文献类型：
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作者：
Kashef,Kimia;Lee,ClementM;Ha,JiHee;Reddy,EPremkumar;Dhanasekaran,DannyN
支架蛋白在赋予信号通路特异性和保真度方面发挥着关键作用。 JNK 相互作用亮氨酸拉链蛋白 (JLP) 已被鉴定为参与连接 JNK 信号模块组件的支架蛋白。 Gα12 和 Gα13 分别是异源三聚体 G 蛋白 G12 和 G13 的 α 亚基，可刺激不同细胞类型中的 JNK 模块。在这里，我们报告 Gα13 与 JLP 发生物理相互作用，这种相互作用增强了 Gα13 介导的 JNK 激活。我们还证明了 MCF-7 细胞中 JLP 和 Gα13 之间的内源相互作用。 JLP 相互作用通过其 C 端结构域（称为 GID-JLP）对 α 亚基的 G12 家族具有特异性，跨越氨基酸 1165−1307，并且与野生型 Gα13 相比，这种相互作用在突变或功能激活形式的 Gα13 中更为明显。由 Gα13、JLP 和 JNK 组成的三元复合物的存在表明 JLP 在将 Gα13 束缚到参与 JNK 激活的信号传导成分中发挥着作用。 GID-JLP 的共表达除了减弱 Gα13 刺激的 JNK 活性外，还会破坏三元复合物的形成。这些发现将 JLP 确定为 Gα13 介导的 JNK 信号通路中的一种新型支架蛋白。
Scaffolding proteins play a critical role in conferring specificity and fidelity to signaling pathways. The JNK-interacting leucine zipper protein (JLP) has been identified as a scaffolding protein involved in linking components of the JNK signaling module. Gα12and Gα13, the α-subunits of heterotrimeric G proteins G12 and G13, respectively, stimulate the JNK module in diverse cell types. Here, we report that Gα13physically interacts with JLP, and this interaction enhances Gα13-mediated JNK activation. We also demonstrate endogenous interaction between JLP and Gα13in MCF-7 cells. JLP interaction is specific to the G12 family of α-subunits via its C-terminal domain (termed GID-JLP), spanning amino acids 1165−1307, and this interaction is more pronounced with the mutationally or functionally activated form of Gα13compared to that of wild-type Gα13. The presence of a ternary complex consisting of Gα13, JLP, and JNK suggests a role for JLP in tethering Gα13to the signaling components involved in JNK activation. Coexpression of GID-JLP disrupts ternary complex formation in addition to attenuating Gα13-stimulated JNK activity. These findings identify JLP as a novel scaffolding protein in the Gα13-mediated JNK signaling pathway.